6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)]
- Myelosuppression [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment of gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
The safety of TALZENNA as monotherapy was evaluated in gBRCAm patients with HER2-negative locally advanced or metastatic breast cancer who had previously received no more than 3 lines of chemotherapy for the treatment of locally advanced/metastatic disease. EMBRACA was a randomized, open-label, multi-center study in which 412 patients received either TALZENNA 1 mg once daily (n=286) or a chemotherapy agent (capecitabine, eribulin, gemcitabine, or vinorelbine) of the healthcare provider's choice (n=126) until disease progression or unacceptable toxicity. The median duration of study treatment was 6.1 months in patients who received TALZENNA and 3.9 months in patients who received chemotherapy. Dosing interruptions due to an adverse reaction of any grade occurred in 65% of patients receiving TALZENNA and 50% of those receiving chemotherapy; dose reductions due to any cause occurred in 53% of TALZENNA patients and 40% of chemotherapy patients. Permanent discontinuation due to adverse reactions occurred in 5% of TALZENNA patients and 6% chemotherapy patients.
Table 3 and Table 4 summarize the most common adverse reactions and laboratory abnormalities, respectively, in patients treated with TALZENNA or chemotherapy in the EMBRACA study.
|Adverse Reactions||Grades 1–4||Grade 3||Grade 4||Grades 1–4||Grade 3||Grade 4|
|Abbreviations: AR=adverse reaction; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; N=number of patients.|
|Blood and lymphatic system disorders|
|Metabolism and nutrition disorders|
|Nervous system disorders|
|Skin and subcutaneous tissue disorders|
|General disorders and administration site conditions|
The following adverse reactions have been identified in <20% of the 286 patients receiving TALZENNA, and thus were not included in Table 3: abdominal pain (19%), dizziness (17%), leukopenia (17%), dysgeusia (10%), dyspepsia (10%), stomatitis (8%), and lymphopenia (7%).
|Parameter||Grades 1–4||Grade 3||Grade 4||Grades 1–4||Grade 3||Grade 4|
|Abbreviation: N=number of patients.|
|Decrease in hemoglobin||90||39||0||77||6||0|
|Decrease in leukocytes||84||14||0.3||73||22||2|
|Decrease in neutrophils||68||17||3||70||21||17|
|Decrease in lymphocytes||76||17||0.7||53||8||0.8|
|Decrease in platelets||55||11||4||29||2||0|
|Increase in glucose†||54||2||0||51||2||0|
|Increase in aspartate aminotransferase||37||2||0||48||3||0|
|Increase in alkaline phosphatase||36||2||0||34||2||0|
|Increase in alanine aminotransferase||33||1||0||37||2||0|
|Decrease in calcium||28||1||0||16||0||0|